PubMed Health⌕ Search

Biomedical subjects

A Collier

Publications and source records attributed to A Collier.

At least 55 records · Page 3Linked to original sources
PubMed1989

Evidence against a role for prostaglandins in sustaining renal hyperfiltration in type 1 diabetes mellitus.

The acute effect of inhibition of prostaglandin synthesis with indomethacin 50 mg by mouth on renal haemodynamics has been examined in 8 male Type 1 diabetic patients with elevated glomerular filtration rate who were free of diabetic complications. Renal plasma flow and glomerular filtration rate were measured by constant infusion of para-amino hippurate and polyfructosan, the patients being studied at normoglycaemia. Urinary excretion of prostaglandin E2 fell from 885 +/- 160 to 345 +/- 115 pg min-1, and excretion of 6-keto-prostaglandin F1 alpha fell from 489 +/- 77 to 283 +/- 50 pg min-1. There was no change in renal plasma flow or glomerular filtration rate following indomethacin. The results do not support the hypothesis that increased renal prostaglandin synthesis is a cause of hyperfiltration in diabetes mellitus.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

A trial of the calcium antagonist felodipine in hypertensive type 2 diabetic patients.

Although calcium antagonists may impair insulin release in vitro, clinical studies have produced conflicting results. Felodipine is a highly selective dihydropyridine calcium antagonist effective in the treatment of hypertension. The efficacy of felodipine was assessed in a double-blind randomized placebo cross-over study of 21 Type 2 diabetic patients with primary hypertension, 13 men and 8 women, with an age of 61 (range 46-73) years. Thirteen were controlled on oral hypoglycaemic therapy and 8 on diet alone. Mean (SD) blood pressure (mmHg) was 176(20)/102(8) after a 2-4 week placebo run-in period, 169(21)/101(8) during the subsequent placebo period compared with 151(15)/88(9) after 4 weeks felodipine therapy (p less than 0.001). Nineteen patients required 5 mg twice daily and 2 patients 10 mg twice daily to achieve a target diastolic pressure of 95 mmHg. Side-effects seen with felodipine included ankle oedema, facial flushing, headache, and dizziness. During oral glucose tolerance tests performed after the felodipine and placebo phases, mean (SD) fasting blood glucose was 9.5(3.1) and 9.0(3.0) mmol l-1, respectively (NS), and the 90 min (peak) blood glucose was 19.1(4.8) and 18.1(4.8) mmol l-1, respectively (NS). Glycosylated haemoglobin and fructosamine concentrations likewise showed no significant changes.

Apolipoproteins↗
PubMed1989

Limited joint mobility, Dupuytren's contracture and retinopathy in type 1 diabetes: association with cigarette smoking.

To examine the associations between cigarette smoking, connective tissue changes, and diabetic retinopathy, a detailed smoking history was elicited from 150 normotensive non-diabetic subjects, and from 266 randomly selected adult patients with Type 1 diabetes, after examination for limited joint mobility, Dupuytren's contracture, and diabetic retinopathy. Mean insulin dose and current glycosylated haemoglobin concentrations were comparable in diabetic smokers and non-smokers. The historical duration of smoking correlated with the duration of diabetes (r = 0.72, p less than 0.001). In diabetic patients limited joint mobility was positively associated with retinopathy, being found in 73/147 (50%) patients with retinopathy compared with 20/114 (18%) without retinopathy (chi 2 = 28.9, p less than 0.001), and also with Dupuytren's contracture, 19/34 (56%) of patients with limited joint mobility having Dupuytren's contracture, compared with 76/232 (33%) of patients without Dupuytren's contracture (chi 2 = 7.05, p less than 0.01). Limited joint mobility was observed in 50% of diabetic smokers compared with 25% of non-smokers (odds ratio = 2.87 (corrected for diabetes duration), 95% confidence interval 1.64-5.01). Diabetic retinopathy was weakly associated with smoking (odds ratio 1.09; 95% confidence interval 0.60-1.96). There was however an increased prevalence of background retinopathy among male smokers (50% vs 29%; chi 2 = 6.88, p less than 0.01). In non-diabetic males limited joint mobility was observed in 37% of smokers but only in 11% of non-smokers (NS), while 33% of smokers and 8% of non-smokers had Dupuytren's contracture (p = 0.012). These results suggest that cigarette smoking contributes to the development of extra-articular connective tissue changes in both diabetic patients and non-diabetic subjects, and possibly to the development of diabetic retinopathy.

Adult↗
PubMed1989

Functional and ligand binding studies suggest heterogeneity of platelet prostacyclin receptors.

1. This study describes attempts to compare prostacyclin (IP-) receptors in human, pig, horse, rabbit and rat platelets and in circular muscle of human, rabbit and dog mesenteric and pig gastroepiploic arteries. Three stable prostacyclin analogues, iloprost, cicaprost and 6a-carba-prostacyclin (6a-carba-PGI2) and a prostaglandin endoperoxide analogue EP 157 (previously shown to mimic prostacyclin on human platelets) were used. 2. Our main conclusion is that prostacyclin receptors on human, pig and horse platelets are similar in nature, but distinct from those on rabbit and rat platelets. Functional studies (inhibition of aggregation) showed that iloprost and cicaprost always had similar potencies whereas 6a-carba PGI2 was much more potent than EP 157 on rabbit and rat platelets (300 and 1000 fold on a molar basis) compared with human, pig and horse platelets (2, 7 and 7 fold respectively). Measurement of initial rates of cyclic AMP production confirmed these orders of potency. 3. Although pig platelets were quite sensitive to inhibition by EP 157 (threshold = 10 nM in some experiments), maximal inhibition of aggregation was not always achieved (20 microM). EP 157 also produced only small elevations of cyclic AMP and inhibited rises in cyclic AMP induced by iloprost. It is possible that EP 157 has a lower efficacy than iloprost at the IP-receptor and on pig platelets it can sometimes act as a partial agonist. 4. Human, pig and horse platelet membranes bound [3H]-iloprost at 30 degrees C and this binding was inhibited by the four prostanoids. On human and pig membranes the order of potency was cicaprost = iloprost greater than 6a-carba PGI2 greater than EP 157. The order of potency may be similar on horse platelet membranes, but the analysis is complicated by the presence of a second component of [3H]-iloprost binding that is inhibited by iloprost and 6a-carba PGI2 but not by cicaprost. This binding may be due to the presence of an EP1-receptor, since iloprost and 6a-carba PGI2 but not cicaprost are known to have potent EP1-receptor agonist actions on smooth muscle preparations. IC50 values for cicaprost inhibition on human, pig and horse membranes were 110, 90 and 165 nM respectively. The need for IP-receptor radioligands of greater specificity is apparent from these studies. 5. Minimal binding of [3H]-iloprost to rabbit and rat platelet membranes was obtained at 30 degrees C. Lowering the incubation temperature to 4 degrees C and ensuring that the temperature did not rise during the filtration process increased binding and allowed inhibition curves to be obtained. The results suggest a lower binding affinity for [3H]-iloprost, associated with a higher dissociation rate for the radioligand-receptor complex. IC50 values for cicaprost were 900nm for rabbit and 640nm for rat platelets. In a similar manner to horse platelet membranes, the presence of a second binding site for [3H]-iloprost was detected on rabbit platelet membranes. 6. Sensitivity to the relaxant action of iloprost on the arterial smooth muscle preparations decreased in the order: human mesenteric, dog mesenteric, rabbit mesenteric, pig gastro-epiploic. Cicaprost was always slightly more potent than iloprost (1.2-2.8 fold). On the pig vessel preparation 6a-carba PGI2 did not produce complete relaxation. The possibility that this is due to an opposing contractile action mediated via EP1 or EP3 receptors is discussed. 7. EP 157 relaxed the human, pig and rabbit arterial preparations at concentrations 100-200 times those of iloprost. This correlates well with its IP-receptor agonist potency on human, pig and horse platelets. The results obtained with EP 157 further demonstrate the potential difficulties in separating platelet inhibitory and vasodilator properties of prostacyclin mimetics in man.

Animals↗
PubMed1989

An infectious aetiology of insulin-dependent diabetes mellitus? Role of the secretor status.

Studies of patients with insulin-dependent diabetes and their families have shown increased incidences of HLA markers B8, B15, DR3 and DR4. While these genetic predispositions are obviously important, additional factors such as environmental influences are presumed to trigger the events leading to the development of diabetes. Infectious triggers, in particular several viruses, have been suggested. The evidence from epidemiological and in vitro studies for a viral aetiology is summarized here. The significance of the recent finding of an increased proportion of non-secretors among patients with insulin-dependent diabetes is discussed in the context of other 'autoimmune' diseases for which infectious aetiologies have been proposed.

ABO Blood-Group System↗
PubMed1989

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult↗
PubMed1989

Blood group, secretor status and oral carriage of yeasts among patients with diabetes mellitus.

The inability to secrete the water-soluble glycoprotein form of the ABO blood group antigens is a genetic characteristic associated with susceptibility to superficial fungal infections and also insulin-dependent diabetes mellitus (IDDM). As oral carriage of Candida albicans in healthy adults is associated with non-secretion, we examined oral carriage of yeasts among 275 patients attending diabetic outpatient clinics, 137 with IDDM and 138 with non-insulin dependent diabetes mellitus (NIDDM) with reference to ABO blood group, secretor status and yeast species. Of the 166 yeast isolates, 109 (66.7%) were C. albicans, a lower proportion compared with 94% reported for healthy individuals. There was no association between ABO blood group and carriage. There was no increase in the proportion of non-secretor carriers of C. albicans among patients with IDDM; but among those with NIDDM, 44% of non-secretors were carriers compared with 21% who were non-carriers (p less than 0.01). The results are discussed in the context of host-parasite interactions influencing colonization.

ABO Blood-Group System↗
PubMed1989

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult↗
PubMed1988

Plasma alkaline phosphatase isoenzymes in diabetes mellitus.

Alkaline phosphatase (ALP) isoenzymes were measured in type 1 diabetics, type 2 diabetics and in a non-diabetic control group. Within the diabetics and the control group, intestinal ALP activity was significantly higher in BO secretors than A secretors or ABO non-secretors. There was no difference in intestinal ALP activity between type 1 and type 2 diabetics but the diabetics had a significantly higher activity of this isoenzyme than the corresponding blood group/secretor status category of the control group. Liver ALP was significantly higher in the diabetics compared with the control group. Bone ALP showed no significant difference between the diabetics and the control group.

Adult↗
PubMed1988

Somatosensory and visual evoked potentials in insulin-dependent diabetics with mild peripheral neuropathy.

Using somatosensory and visual evoked potential techniques we have looked for evidence of central neuropathy in a group of insulin-dependent diabetics with mild peripheral neuropathy. The N9, N13, and N20 components of the somatosensory evoked potential were significantly (P less than 0.001) delayed in the diabetic group compared with the control subjects. There was a small but non-significant increase in the interpeak N13-9 and N20-13 latencies in the diabetic group. The visual evoked potential (P100) showed a small but insignificant delay. The delay in cerebral evoked potentials was mostly attributable to peripheral neuropathic damage and no firm evidence was obtained in favour of central diabetic neuropathy.

Adult↗
PubMed1988

Effectiveness of acarbose, an alpha-glucosidase inhibitor, in uncontrolled non-obese non-insulin dependent diabetes.

The effect of acarbose, an alpha-glucosidase inhibitor, on glycaemic control, was compared with placebo in a double-blind, randomised, group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn. There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea. There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose (11.3% and 12.4% respectively) or the placebo group (10.6% and 12.2% respectively). In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered. This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone.

Acarbose↗
PubMed1988

Hyperandrogenism, insulin resistance, acanthosis nigricans, and systemic lupus erythematosis associated with insulin receptor antibodies.

We report a young woman with systemic lupus erythematosis (SLE) who developed diabetes secondary to extreme insulin resistance, associated with severe hyperandrogenism and acanthosis nigricans. Her insulin resistance was found to be associated with high titers of insulin receptor antibodies. The hyperandrogenism has been favourably influenced by cyclical treatment with cyproterone acetate and ethinyl oestradiol, but the insulin resistance and acanthosis nigricans have remained unmodified after 15 months of follow up.

Acanthosis Nigricans↗
PubMed1988

Increased urinary excretion of glycosaminoglycans in insulin-dependent diabetic patients with limited joint mobility.

Urinary excretion of glycosaminoglycans (GAG) was measured in 24-h specimens collected from 27 insulin-dependent male diabetic patients and 22 healthy males of similar ages. Excretion relative to creatinine was increased by 35% in the diabetic group as a whole (p less than 0.02). Twelve patients with limited joint mobility (cheiroarthropathy) formed a subgroup with high excretion (69% above controls), those without limited joint mobility being similar to controls. There was no correlation of retinopathy with GAG excretion.

Adult↗
PubMed1988

The importance of the time interval between insulin injection and breakfast in determining postprandial glycaemic control--a comparison between human and porcine insulin.

This study assessed the effect of the time interval between insulin injection and breakfast in determining subsequent postprandial glycaemic control and also whether this differed between highly purified porcine insulin and human insulin (crb) in six diabetic patients (age range 24-36 years, duration of diabetes greater than 10 years) usually treated with twice daily Actrapid MC and Monotard MC and with stable insulin requirements and diabetic control. On separate mornings each patient was given, after an overnight fast, their usual dose of either Actrapid MC and Monotard MC or Humulin S and Humulin Zn injected 5, 20, or 40 min before a standard breakfast. The postprandial glycaemic profile was not significantly different at any of the three time intervals with Actrapid MC and Monotard MC. However, with the human insulin the profile was significantly better at the 40 min interval than at the 5 min interval (p less than 0.05) and this was also better than any of the profiles with the porcine insulin, there being a significant difference between the two types of insulin (p less than 0.05). These findings suggest that the time interval between insulin injection and breakfast may be more important with human insulin than with porcine insulin.

Adult↗
PubMed1988

Reduced free radical activity detected by decreased diene conjugates in insulin-dependent diabetic patients.

Free radicals are unstable chemical species which react with and oxidize adjacent molecules, particularly polyunsaturated lipids. The diene-conjugated non-peroxide isomer of linoleic acid (PL-9,11-LA') has been identified as the main diene-conjugated compound in plasma, and is a probable marker of free radical activity. The aim of the current study was to determine whether the level of PL-9,11-LA', measured by HPLC, is altered in insulin-dependent diabetes, and to investigate whether any abnormality demonstrated correlated with microvascular disease in the form of retinopathy. There was no difference in the concentrations of linoleic acid between the diabetic and control groups (422(129) vs 402(81) (SD) mumol l-1). However, the concentration of PL-9,11-LA' was significantly reduced in the diabetic group compared with control group (15.6(6.7) vs 19.3(3.9) mumol l-1, p less than 0.01), with the molar ratio of PL-9,11-LA':linoleic acid x 100 similarly reduced (3.8(1.3) vs 5.0(1.6)%, p less than 0.005). This study does not support the concept that free radicals play a significant role in the development of diabetic vascular disease.

Adult↗
PubMed1988

Are reduced lung volumes in IDDM due to defect in connective tissue?

Lung volumes were measured by spirometry and helium-dilution technique in 28 young adult men with insulin-dependent diabetes mellitus (IDDM) of long duration and compared with 16 age- and height-matched adult men without diabetes. Reduced values for forced expiratory volume at 1 s, vital capacity, functional residual capacity, total lung capacity, residual volume, and single-breath carbon monoxide transfer factor were found for the IDDM patients compared to the control subjects. The results are consistent with reduced lung volumes in IDDM patients and did not correlate with the presence or absence of mild cheiroarthropathy but may relate to duration of diabetes.

Adult↗
PubMed1988

Secretor state and complement levels (C3 and C4) in insulin dependent diabetes mellitus.

Lower levels of C3 and C4 components of the complement system have been reported for patients with insulin dependent diabetes mellitus (IDDM) but not among those with non-insulin dependent diabetes (NIDDM). We have found a significantly higher proportion of patients who are non-secretors of the ABO blood group antigens among patients with IDDM but not among those with NIDDM. As the gene that controls secretion of these antigens is in the same linkage group as that for the C3 complement component, we compared the levels of C3 and C4 of patients with IDDM by secretor state. The mean level of C3c for 45 non-secretors (75.2 IU/ml) was significantly lower than that found for 59 secretors (86.4 IU/ml) (p less than 0.025). The level of C4 among non-secretors (77.1 IU/ml) was also significantly lower than that of secretors (96.3 IU/ml) (p less than 0.025). The significance of these observations is discussed.

ABO Blood-Group System↗